Virus against virus: Members of the CRC developed an agent directly targeting both SARS-CoV-2 particles and infected cells

Since the onset of the COVID-19 pandemic, numerous treatments and vaccines have been developed to combat the virus. These interventions, including monoclonal antibodies and mRNA vaccines, have significantly reduced the number of severe and fatal cases. They primarily act by inhibiting viral entry or replication in human target cells. However, a growing concern is the persistence of SARS-CoV-2, particularly in individuals with a compromised immune system due to factors such as age, autoimmune diseases, or comorbidities like diabetes. These prolonged infections are now recognized as one of the contributing factors to Long COVID. Consequently, there is a need for treatments that not only target the virus but also allow the elimination of SARS-CoV-2-infected cells.

In an interdisciplinary study, published in the Nature group journal Signal Transduction and Targeted Therapy, members of the CRC 1279 in cooperation with the Institute of Pathology at Ulm University, show that Vesicular Stomatitis Virus (VSVΔG) particles carrying the SARS-CoV-2 receptor, Angiotensin-Converting Enzyme 2 (ACE2), allow specific targeting of both SARS-CoV-2 virions and infected cells.

“Usually, VSVΔG particles are pseudotyped with viral Spikes proteins to determine e.g. neutralizing antibody titers against SARS-CoV-2. However, reversing this system and equipping VSVΔG particles with the ACE2 receptor enables them to neutralize SARS-CoV-2 as well as related viruses that utilize ACE2 to infect human cells,” explains Dr. Fabian Zech, first and co-corresponding author of the study. “Importantly, these particles also super-infect and eliminate SARS-CoV-2 infected cells, thereby preventing the production of new infectious SARS-CoV-2 particles."

The safety and efficacy of the ACE2-carrying particles was further validated in the Syrian golden hamster model. Pre-treatment with VSVΔG-ACE2 particles significantly reduced lung-associated SARS-CoV-2 after infection. The development of an antiviral agent that directly targets SARS-CoV-2 infected cells represents a major leap forward in combating Long COVID.

Doi: 10.1038/s41392-023-01492-7